Mg Of Sotalol Research Articles

Home Sotalol Initiation for the Management of Atrial and Ventricular Arrhythmias Using Remote Electrocardiographic Monitoring.

Sotalol is a class III antiarrhythmic drug used for the management of patients with atrial fibrillation to maintain sinus rhythm. Sotalol-induced QT interval prolongation can be proarrhythmic and is conventionally initiated in an inpatient setting where routine electrocardiographic (ECG) monitoring is available while sotalol reaches the steady state. The emergence of cellular-compatible home ECG devices, such as AliveCor's Kardia Mobile 6L, which offers 6-lead ECG, has made it possible to accurately measure QT intervals outside the hospital. This study aimed to evaluate the safety, feasibility, and patient adherence to protocol-driven, pharmacist-led outpatient sotalol initiation using the Kardia Mobile 6L for remote ECG monitoring and to compare these outcomes with patients completing inpatient sotalol protocol for initiation. Patients who underwent outpatient sotalol initiation through an antiarrhythmic clinic for the treatment of both atrial and ventricular arrhythmias over a period of approximately 3 years, from September 1, 2020, to June 16, 2023, were retrospectively reviewed and compared with a cohort of inpatients initiated on sotalol. The outpatient cohort had a minimum longitudinal follow-up of 90days. A total of 263 patients using the outpatient sotalol initiation protocol were compared with 28 age- and sex-matched inpatients who underwent inpatient sotalol initiation. The outpatient cohort included 179 men (68%), with an age of 68.8 ± 10.1 years, CHA2DS2-VASc score of 3.48 ± 1.43, baseline 12-lead QTc interval of 440.77 ± 33.42ms, and a left ventricular ejection fraction of 57.4% ± 9.23%. Outpatients were started on a median (minimum-maximum) dose of 120 (80-160) mg of sotalol twice a day (120-mg dose; n=227; 86.3%) and ended at a median (minimum-maximum) dose of 120 (60-160) mg twice a day (120-mg dose; n=217; 82.5%). The proportions of patients prescribed low-, moderate-, or high-dose sotalol twice a day (60mg, 80mg, 120mg, and 160mg) at the end of initiation were similar between the inpatient and outpatient groups (P=0.5). The majority (98.9%; 260 of 263) of patients completed the 3-day outpatient initiation. Outpatient adherence was high during the 3-day initiation period among patients with varied age and socioeconomic background; 258 patients (98.1%) completed the ECG on day 1, and 240 (91.3%) completed the ECG on day 3. No significant QTc interval prolongation was observed during the outpatient postinitiation study period. There were similar sotalol discontinuation rates within 30days of initiation in the inpatient vs outpatient cohorts (7% vs 8%; P > 0.90). A total of 17 (6.5%) patients stopped sotalol because of symptomatic bradycardia, and 1 death was observed over a 90-day follow-up period in the outpatient cohort. Outpatient initiation of sotalol through a protocol-driven, pharmacist-led antiarrhythmic clinic is feasible and safe, with high adherence rates in a diverse range of patients using personal remote ECG.

Influence of baseline QTc on sotalol-induced prolongation of ventricular repolarization in men and women.

The extent of sotalol-induced QTc prolongation on the electrocardiogram, is variable among subjects and influenced by sex. However, the influence of baseline QTc on the extent of drug-induced QTc prolongation remains unclear. This was studied around peak plasma concentration in a large cohort of 376 healthy male and 614 healthy female subjects who received 80 mg of sotalol orally. Baseline QTc was 379 ± 16 ms in men and 393 ± 15 ms in women (P< .0001). The change in QTc from baseline was highly variable among both sexes and was greater in women than in men (26.5± 13.2 vs.13.0±10.8ms; P< .0001). The slope of the regression line between QTc on sotalol and baseline QTc did not significantly differ from unity in men and in women, indicating that the extent of QTc prolongation with sotalol was not influenced by baseline QTc. Assessing QTc after administration of an IKr blocker may be more important than measuring a baseline QTc.

Automatic analysis of cardiac repolarization morphology using Gaussian mesa function modeling

A novel fully automated method for wave identification and extraction from electrocardiogram (ECG) waveforms is presented. This approach implements the combined use of a new machine-learning algorithm and of specified parameterized functions called Gaussian mesa functions (GMFs). Individual cardiac cycle waveforms are broken up into GMFs using a generalized orthogonal forward regression algorithm; each individual GMF is subsequently identified (wave labeling) and analyzed for feature and morphologic extraction. The GMF associated with the repolarization waveform of the main vector lead, based on principal components analysis, was analyzed, and a set of morphologic parameters were derived under 2 experimental settings: first, in 100 digital 12-lead ECG Holter recordings acquired during three 24-hour periods (baseline and after 160 and 320 mg of sotalol) from 38 healthy subjects; second, in drug-free 12-lead resting ECGs from 100 genotyped long QT syndrome (LQTS) patients (50 each with LQT1 and LQT2). QT-interval duration was measured using an on-screen method applied to the global representative beats and reviewed by a senior cardiologist. QTci (individual correction) was used for analysis. All parameters in the sotalol test showed highly significant differences between the time of peak plasma concentration (Tmax) and baseline ECGs; however, the dynamic pattern of individual parameters followed different patterns. The LQTS test confirmed the results of the sotalol test, showing that GMF-based repolarization parameters were strongly modified as compared with healthy controls. In particular, T-wave width and descending phase of repolarization were more prolonged in LQT2 compared to LQT1.

Impaired T‐Amplitude Adaptation to Heart Rate Characterizes IKr Inhibition in the Congenital and Acquired Forms of the Long QT Syndrome

The QTc interval prolongation is not a perfect surrogate marker of the presence of an increased risk for arrhythmic events. In the search for alternative markers, we investigated the T-amplitude and QT interval adaptation to heart rate (HR) in patients with the congenital long QT syndrome (LQTS) and individuals with sotalol-induced QT prolongation. Our investigation is based on the analysis of continuous 12-lead digital Holter recordings in: 49 LQT1 carriers, 25 LQT2 carriers, 37 healthy individuals off drugs and on 160 mg of sotalol, and 21 of them also on 320 mg of sotalol. The Holter recordings were used to investigate repolarization parameters and their HR dependency. A loss of HR dependency of the T-amplitude was found as a common feature in individuals with impaired I(kr) kinetics: LQT2 carriers and subjects on sotalol. The T-amplitude/RR slope was significantly (P < 0.05) flatter in LQT2 (0.31 +/- 0.27 microV/ms) than in both LQT1 (0.62 +/- 0.40 microV/ms) and healthy individuals (0.55 +/- 0.29 microV/ms). A dose-dependent reduction of the T-amplitude/RR slope was also observed in subjects on sotalol (160 mg dose: 0.26 +/- 0.19 microV/ms; 320 mg dose: 0.21 +/- 0.14 microV/ms). The QT/RR slope was less effective than T-amplitude/RR slope in differentiating between congenital and drug-induced repolarization delay. Impaired adaptation of T-amplitude to changing HR is a common electrocardiographic feature associated with KCNH2 mutation and I(kr) blockade by sotalol. This ECG marker may play an important role in the future of the assessment of the penetrance of KCNH2 mutation and the identification of a drug effect on the I(kr) kinetics.

Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis

BackgroundAtrial fibrillation can occur in up to 40% of patients undergoing coronary surgery.MethodsWe retrospectively analysed 103 consecutive coronary surgery patients under the care of one surgeon between April 2003 and September 2003. These patients received 40 mg of sotalol orally twice daily from the first post-operative day for 6 weeks and 2 g of magnesium intravenously immediately post surgery and on the first post-operative day. We developed a propensity score for the probability of receiving sotalol and magnesium after coronary surgery. 89 patients from the sotalol and magnesium group were successfully matched with 89 unique coronary surgery patients who did not receive either sotalol or magnesium with an identical propensity score.ResultsPreoperative characteristics were well matched between groups. There was no significant difference with respect to in-hospital mortality between groups (sotalol and magnesium 1.1% versus control 4.5%; p = 0.17). The incidence of atrial fibrillation in the sotalol and magnesium group was 13.5% compared to 27.0% in the controls (p = 0.025).ConclusionThe combination of sotalol and magnesium can significantly reduce the incidence of post-operative atrial fibrillation following coronary surgery.

Two cases of torsades de pointes caused by sotalol therapy

An 84 year old woman developed complete atrioventricular block with a ventricular escape rhythm of 34 beats per minute after taking two tablets of sotalol (=320 mg) for sudden atrial fibrillation with fast ventricular response. During emergency transport to hospital ventricular fibrillation occurred which was successfully treated by electrical defibrillation. On admission neither her medical history nor ECG could reveal evidence of ischaemic heart disease or heart failure. Concomitant medication consisted of amlodipine 5mg once a day and dimetindene for itching. During her stay in the emergency department and hospitalisation, a total atrioventricular block with slow ventricular escape rhythm was noted associated with pause-dependent torsades de pointes (QT=490 ms) (Fig. 1). Sotalol therapy was discontinued and an idiopathic hypokalemia of 2.4 meq l was corrected. No valid explanation for this hypokalemia could be found. Except for the potassium disorder, haematology and biochemistry blood values were normal. Creatinine and urea levels were 1.3 and 61 mg dl, respectively. There was a euthyroid status. After therapy with intravenous isoproterenol and magnesium sulphate failed, temporary pacing at 70 beats per minute was initiated. After 12 days the patient was discharged from hospital uneventfully and the atrial fibrillation was managed conservatively with digitalis and aspirin. A 73 year old lady on chronic haemodialysis for terminal nephropathy was admitted to the emergency department in March, 1996 because of sudden atrial tachycardia with a fast ventricular rate. Her medical history revealed a cerebrovascular accident in 1985, with arterial hypertension. In 1986 she developed analgesic nephropathy. After 5 years, she had a temporary nephrostomy after renal papillary necrosis and right ureteral obstruction. In 1995 she was haemodialysed for the first time: urea and creatinine levels then were 99 and 7.1 mg dl, respectively. Potassium level reached 4.6 meq l. During her stay in the emergency room, she was given 160 mg of sotalol orally. An echocardiographic examination showed right atrial and ventricular enlargement, further with left atrial enlargement. The left ventricle had normal dimensions with global and regional contractility preserved. There was no left ventricular hypertrophy nor pericardial effusion. Discrete mitral, aortic, tricuspidal and pulmonary valve insufficiency were observed. Eventually, examination revealed pulmonary hypertension. On admission, blood biochemistry showed a urea level of 35 mg dl, a creatinine level of 3.2 mg dl with a potassium of 4.7 meq l and * Corresponding author. Tel.: +32-53-724461; fax: +32-53724505; e-mail: Ignace.Demeyer@olvz-aalst.be.

Prevention of Supraventricular Tachyarrhythmias After Open Heart Operation by Low-Dose Sotalol: A Prospective, Double-Blind, Randomized, Placebo-Controlled Study

Background. The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. Methods. Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. Results. There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 ± 5 days in patients with supraventricular arrhythmias, versus 9.5 ± 2.4 days in patients without it ( p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 ± 12 beats/min versus 85 ± 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 ± 0.03 second; placebo group, 0.43 ± 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients ( p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. Conclusions. Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.

Interaction between sotalol and an antacid preparation

Aims The aim of the study was to investigate the pharmacokinetic interaction between sotalol and antacids, and its pharmacodynamic relevance. Methods In a randomized cross‐over design with three treatment groups, six healthy volunteers received orally either 160 mg of sotalol alone (phase 1), or 160 mg sotalol plus 20 ml of a suspension of an antacid (MAH; magnesium hydroxide (1200 mg) and aluminium oxide (1800 mg)) (phase 2) or 160 mg sotalol plus the antacid given 2 h after sotalol administration (phase 3). Heart rate and plasma sotalol concentrations were measured before and 1, 2, 3, 4, 6, 8, 12 and 24 h after sotalol administration. Urinary sotalol excretion was measured for 24 h after sotalol application. Results Cmax of sotalol decreased from 1.22±0.22 mg l−1 (phase 1) to 0.89±0.29 mg l−1 (phase 2) and increased again to 1.27±0.18 mg l−1 in phase 3. A similar significant change was noted in AUC (15.6±2.75 mg l−1 , 12.3±3.04 mg h l−1 and 15.0±2.06 mg l−1 ) and in the amount of cumulative urinary excretion (79.2±11.1 mg, 72.1±11.2 mg and 80.6±7.9 mg), respectively. tmax and elimination half‐life (t1/2,z) of sotalol remained unchanged in the presence of MAH. After combined administration with MAH, the area under the heart rate curve of sotalol was reduced between 0 and 4 h when compared across treatments. Conclusions Combined administration of sotalol and MAH decreased the serum sotalol levels. The interaction can be avoided by a two hour interval between application of these drugs.

Determination of sotalol in human cardiac tissue by high-performance liquid chromatography

A sensitive and quantitative reversed-phase HPLC method for the analysis of d,l-sotalol in human atria, ventricles, blood and plasma was developed. Sotalol was determined in about 100 mg of human right atria, left ventricles, and in 500 μl of blood and plasma samples of patients undergoing coronary bypass surgery or heart transplantation. Patients were taking 80–160 mg of sotalol as an antiarrhythmic agent. Atenolol was used as an internal standard certifying high precision of measurement. Sotalol blood and plasma concentrations correlated linearly to the obtained signals from 26.5 ng/ml to 2.12 μg/ml. Sotalol tissue concentrations showed linearity between 0.27 ng/mg and 10.6 ng/mg wet weight. The limit of quantitation was 0.27 ng/mg at a signal-to-noise ratio of 10. Sotalol was extracted from homogenized tissue with a buffer solution (pH 9) and the remaining pellet was extracted with methanol. The methanol extract was evaporated under nitrogen and reconstituted in buffer (pH 3). The whole extract was cleaned by solid-phase column extraction, eluted with methanol, evaporated again, reconstituted in the mobile phase (acetonitrile-15 m M potassium phosphate buffer pH 3, 17:83, v/v) and injected onto the HPLC column (Spherisorb C 6 column, 5 μm,, 150×4.6 mm I.D). For the detection of sotalol, the UV wavelength was set to 230 nm. Recoveries of sotalol and atenolol in atria and ventricles were 65.6 and 75.0%, respectively. Intra- and inter-assay coefficients of variation for tissue concentrations were 3.38 and 6.14%, respectively. Intra- and inter-assay accuracy for determined tissue sotalol concentrations were 94.9±6.3 and 99.6±4.1%.

Long-term efficacy of d/l sotalol in patients with sustained ventricular tachycardia refractory to class I antiarrhythmic drugs.

The efficacy of d/l sotalol was investigated in 50 patients (43 men, seven women; 33 with coronary artery disease, 15 with dilated cardiomyopathy; ejection fraction 33 +/- 10%) with inducible sustained ventricular tachycardia. Before d/l sotalol a mean of 2 +/- 1 (1 to 4) class I antiarrhythmic drugs were ineffective. In 24 patients (48%) oral d/l sotalol (320 +/- 47 mg.day-1) prevented induction of the ventricular tachycardia; in 23 patients the ventricular tachycardia remained inducible (d/l sotalol 326 +/- 50 mg.day-1). The electrophysiological effects of d/l sotalol did not differ between patients in whom d/l sotalol prevented induction of ventricular tachycardia and those in whom the ventricular tachycardia remained inducible. In two patients, torsade des pointes developed after oral application of d/l sotalol; one patient suffered from severe hypotension even with 80 mg of sotalol per day. During long-term follow-up (27 +/- 12 months) 5/24 patients (21%) had a non-fatal recurrence of ventricular tachycardia (1 week to 21 months), one patient died suddenly and another from progressive heart failure. In patients in whom the ventricular tachycardia could be induced despite oral application of d/l sotalol, control of the ventricular tachyarrhythmia was attempted by the use of sotalol in combination with mexiletine (n = 2), amiodarone (n = 9), catheter ablation (n = 2), antitachycardia surgery (n = 1) or the implantation of an automatic cardioverter defibrillator (n = 12). Recurrence of ventricular tachycardia was observed in four patients without an implanted cardioverter defibrillator. Seven out of 12 patients with an implanted cardioverter defibrillator received appropriate shocks or successful antitachycardia pacing. Although no patient died suddenly, overall mortality was 17% in this group. It is concluded that d/l sotalol is highly effective in the suppression of sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation. However during a mean follow-up of 27 +/- 12 months a recurrence of ventricular tachycardia was seen in 21% of patients, and one patient died suddenly.

Effectiveness of sotalol in preventing supraventricular tachyarrhythmias shortly after coronary artery bypass grafting

To investigate the effectiveness and safety of low-dose sotalol (a class III antiarrhythmic β-blocking agent) in the prevention of supraventricular tachyarrhythmias (SVTs) and to identify predictors for the occurrence of these arrhythmias shortly after coronary artery bypass grafting, 300 consecutive patients were randomized in a double-blind, placebo-controlled fashion. Patients with severely depressed left ventricular function or other contraindications for β blockers were excluded. Beginning at 4 hours and up to the sixth day after surgery, 150 patients received 40 mg of sotalol every 6 hours and 150 patients received placebo every 6 hours. SVT was observed in 24 (16%) of 150 low-dose sotalol- and in 49 (33%) of 150 placebo-treated patients [p < 0.005]. In patients receiving sotalol, atrial fibrillation was the only noted tachyarrhythmia, whereas in the placebo group, 42 (28%) patients had atrial fibrillation, 3 (2%) atrial flutter, 1 (0.7%) atrial tachycardia and 3 (2%) sinus tachycardia. Drug-related adverse effects necessitating discontinuation of the drug were noted in only 2 (1%) sotalol-treated patients and 4 (3%) placebo-treated patients (p = not significant). For both groups, univariate analysis indicated that older age, 1- or 2-vessel coronary artery disease, long bypass (≥150 minutes) and aorta cross-clamp time (≥120 minutes) were predictive variables for the occurrence of SVTs. Multivariate analysis showed that male sex (odds ratio 2.3), 1- or 2-vessel coronary artery disease (odds ratio 2.0) and older age (odds ratio 1.1) were independent risk factors for increased occurrence of postoperative SVT. The prophylactic use of low-dose sotalol [odds ratio 0.3] gave considerable and safe protection against the occurrence of SVTs shortly after coronary artery bypass grafting.

Suppressant effects of conventional beta blockers and sotalol on complex and repetitive ventricular premature complexes

Beta-blocking drugs have been shown to reduce the overall mortality and risk of sudden cardiac death in survivors of acute myocardial infarction. It is not known whether such an effect is mediated by suppression of ventricular premature complexes (VPCs). The circadian rhythmicity of ventricular arrhythmia can also be suppressed by β-blocking drugs, and this may help reduce the risk of sudden cardiac death during the morning hours. Recent studies have also shown that β blockers can provide a safe and effective combination with class IA antiarrhythmic agents when arrhythmias cannot be controlled with class IA agents alone. Sotalol, a nonselective β antagonist, has unique electrophysiologic properties, and several studies have shown it to be more effective than conventional β blockers in suppressing ventricular arrhythmias. However, direct comparative studies of the suppression of VPCs are lacking. In a recent double-Mind, placebo-controlled, parallel study, the antiarrhythmic effects of sotalol and propranolol were compared in 172 patients with >30 VPCs/ hour. After the initial 1-week washout and 1-week placebo period, patients were randomly assigned to either 160 mg of sotalol administered twice daily (76 patients) or 40 mg of propranolol administered 3 times daily (91 patients). Those responding to therapy (decreases >75% VPCs) continued to take these closes, but nonresponders were given higher doses, 320 mg of sotalol twice daily or 80 mg of propranolol 3 times daily, respectively. The baseline mean hourly VPC count, derived from two 24-hour Holter recordings during the placebo phase, was 274 for sotalol and 255 for propranolol patients and was reduced to 54 (80% decrease) for sotalol and 104 (59% decrease) for propranolol-treated patients at 6 weeks (p < 0.002). A significantly greater percentage of patients (56%) responded to sotalol compared with those who responded to propranolol (29%) (p < 0.001). The class III antiarrhythmic activity of sotalol may account for its superiority over propranolol.